IMMUNE CONTROL OF WEST NILE VIRUS QUASISPECIES DYNAMICS

描述（由申请方提供）：RNA病毒在自然界中不作为单一基因组序列存在，而是作为相关序列的混合物存在，称为病毒群或准种。这个建议的目的是表征病毒序列变异的功能性后果的主机内，不同的免疫能力使用西尼罗河病毒作为一个模型。该建议旨在确定I型干扰素反应如何区别地限制病毒生长，这是由遗传同质性与异质性病毒群体引起的疾病。它还解决了I型IFN对WNV基因组进化的影响，从而更好地理解受I型IFN信号传导途径限制的病毒序列和多样性（核苷酸和蛋白质）。更深入地了解I型IFN和病毒群之间的相互作用可以促进限制病毒多样性、免疫逃逸和疾病严重程度的新策略。此外，了解I型IFN如何控制病毒进化可以提高减毒活疫苗的安全性和免疫原性，因为大多数疫苗来自感染性克隆，这是同源病毒的来源。

DESCRIPTION (provided by applicant): RNA viruses do not exist in nature as a single genomic sequence, but rather as an amalgam of related sequences referred to as a viral swarm or quasispecies. This proposal is designed to characterize the functional consequences of virus sequence variation within hosts that vary in immunological competence using WNV as a model. This proposal aims to identify how the type I IFN response differentially restricts viral growth an disease caused by a genetically homogenous versus heterogeneous virus population. It also addresses the effect of type I IFN on the evolution of the WNV genome, leading to a better understanding of the viral sequences and diversity (both nucleotide and protein) that are restricted by the type I IFN signaling pathway. A greater understanding of the interactions between type I IFN and a viral swarm could promote novel strategies to limit viral diversity, immune escape, and disease severity. In addition, understanding how type I IFN controls viral evolution could promote increased safety and immunogenicity of live attenuated vaccines, as most vaccines are derived from infectious clones, a source of homogenous virus.